Characterization of the role of Cripto in trophoblast cells during placental development
Bibliographic record
Abstract
Cripto, a member of the Epidermal Growth Factor-Cripto/FRL-1/Cryptic (EGF-CFC1) protein family, plays a crucial role in embryonic development.In addition to embryonic expression, Cripto is expressed in extraembryonic tissues including the various trophoblast cell subtypes spongiotrophoblast and labyrinth sinusoidal giant cells.In human studies, dysregulation of Cripto expression adversely affects placental development and function.Previous findings have reported that Cripto expression is significantly higher in placental pathologies such as placenta accreta and placenta previa compared to normal placentas.Additionally, expression analysis of the EGF-CFC1 gene family demonstrate genetic associations with recurrent pregnancy loss.During mouse embryonic development, the homozygous deletion of Cripto in the inner cell mass is embryonic lethal between days 7.5 and 10.5; however, the deletion of Cripto in the extraembryonic trophectoderm, is yet to be studied.Thus, based on the expression of Cripto in the trophectoderm, and its deregulated expression in pregnancy complications, we hypothesize that Cripto plays an important role in placental development and function.To address that, we generated a Cripto knockout exclusively in mouse TE cells using Tat-Cre recombinant protein.Tat-Cre optimization protocol involving the mating of Cripto floxed females with homozygous mTmG males showed high efficiency of cre-recombination exclusively in TE cells.Following the optimization of the model for knocking out Cripto, homozygous Cripto floxed Tat-Cre-treated embryos were then transferred into uteri of pseudopregnant control mice for continued development.Dissections of the knockout implantation sites at day 10.5 exhibited significantly decreased implantation site size and placental thickness compared to the control sites.Furthermore, hematoxylin and eosin staining revealed positional deviated placentas according to the AM-M axis in the knockouts compared to the controls.Immunofluorescence staining with TE List of Abbreviations BMP Bone morphogenetic protein Cdx2 Caudal type homeobox 2 EGF-CFC Epidermal growth factor-Cripto1/FRL1/Cryptic Fzd5 Frizzled class receptor 5 GCM1 Glial cells missing-1 GDF1/3 Growth and differentiation factors 1/3 ICM Inner cell mass IGFBP1 Insulin-like growth factor-binding protein 1 IUGR Intrauterine growth restriction Mash2 Mouse achaete-scute homolog-2 PCR Polymerase chain reaction PL Placental Lactogen PgrCre Cre recombinase driven under the Progesterone Receptor PrE Primitive endoderm Stox1 Storkhead box 1 TBS Tris buffered saline TE Trophectoderm TGC Trophoblast giant cells TGF𝜷 Transforming growth factor beta TDGF1 Teratocarcinoma-derived growth factor-1 Tpbpa Trophoblast specific protein alpha VEGF Vascular endothelial growth factor
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".